The proposed research will characterize neuronal activity induced by pain and determine how this activity is modulated by expectation of pain. Through identification of regions of the central nervous system in which neural activity predicts perception of pain, the proposed research will ascertain biomarkers for the clinical diagnosis of pain. The overall aims are: 1) to characterize changes in neuronal activity that encode the intensity of pain, 2) to elucidate expectation-induced changes in pain-related neural activity, and 3) to identify biomarkers for the intensity of experienced pain. To achieve these aims, functional magnetic resonance imaging (fMRI) will be used to image the human spinal cord and brain. Recent literature has demonstrated that the intensity of a thermal stimulus is correlated with neuronal activity in the thalamus, cingulate cortex, insula, and primary sensory cortex;these regions of the brain are henceforth referred to as the pain circuit. It has not been demonstrated whether intensity of painful stimulation correlates with neuronal activity in the human spinal cord. In the first proposed experiment it is hypothesized that intensity of painful thermal stimulation will positively correlate with neuronal activity in the dorsal horn of the spine. In a second experiment, subjects will be given a cue prior to the administration of each painful stimulus. It is hypothesized that during expectation of pain, the anticipated intensity of a stimulus will positively correlate with neuronal activity, and that expectation of reduced pain will decrease reported perception of pain as well as the magnitude of fMRI signal recorded for regions of the pain circuit. In a third set of experiments we will test the hypothesis that the strength of the fMRI signal recorded from the pain circuit can predict the subjective experience of pain. Pain negatively impacts quality of life and is a difficult condition to diagnose and treat because clinicians lack objective means of measuring a patient's experiences of pain. The proposed experiments will characterize neuronal activity induced by pain and determine how this activity is modulated by expectation. By identifying regions of the central nervous system that can predict the subjective magnitude of experienced pain, the proposed research will lead to identification of biomarkers for the clinical diagnosis of pain and advance our understanding of individual differences in pain perception.